Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0014070 (
encephalomyelitis
)
13,017
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SKAP-HOM is a cytosolic adaptor protein representing a specific substrate for the Src family protein tyrosine kinase Fyn. Previously, several groups have provided experimental evidence that SKAP-HOM (most likely in cooperation with the cytosolic adaptor protein
ADAP
) is involved in regulating leukocyte adhesion. To further assess the physiological role of SKAP-HOM, we investigated the immune system of SKAP-HOM-deficient mice. Our data show that T-cell responses towards a variety of stimuli are unaffected in the absence of SKAP-HOM. Similarly, B-cell receptor (BCR)-mediated total tyrosine phosphorylation and phosphorylation of Erk, p38, and JNK, as well as immunoreceptor-mediated Ca(2+) responses, are normal in SKAP-HOM(-/-) animals. However, despite apparently normal membrane-proximal signaling events, BCR-mediated proliferation is strongly attenuated in the absence of SKAP-HOM(-/-). In addition, adhesion of activated B cells to fibronectin (a ligand for beta1 integrins) as well as to ICAM-1 (a ligand for beta2 integrins) is strongly reduced. In vivo, the loss of SKAP-HOM results in a less severe clinical course of experimental autoimmune
encephalomyelitis
following immunization of mice with the encephalitogenic peptide of MOG (myelin oligodendrocyte glycoprotein). This is accompanied by strongly reduced serum levels of MOG-specific antibodies and lower MOG-specific T-cell responses. In summary, our data suggest that SKAP-HOM is required for proper activation of the immune system, likely by regulating the cross-talk between immunoreceptors and integrins.
...
PMID:Regulation of in vitro and in vivo immune functions by the cytosolic adaptor protein SKAP-HOM. 1613 97
The cytosolic adhesion and degranulation-promoting adapter protein
ADAP
is expressed in various hematopoietic cells including T cells, NK cells, myeloid cells, and platelets but absent in mature B cells. The role of
ADAP
in T cell activation, proliferation and integrin activation is well-accepted. We previously demonstrated that conventional
ADAP
knockout mice show a significantly attenuated course of experimental autoimmune
encephalomyelitis
(EAE). To dissect the impact of different
ADAP
expressing cell populations on the reduced EAE severity, here, we generated lineage-specific conditional knockout mice.
ADAP
was deleted in T cells, myeloid cells, NK cells and platelets, respectively. Specific loss of
ADAP
was confirmed on the protein level. Detailed immunophenotyping was performed to assess the consequence of deletion of
ADAP
with regard to the maturation and distribution of immune cells in primary and secondary lymphoid organs. The analysis showed equivalent results as for conventional
ADAP
knockout mice: impaired thymocyte development in
ADAP
fl/fl
Lck-Cre mice, normal NK cell and myeloid cell distribution in
ADAP
fl/fl
NKp46-Cre mice and
ADAP
fl/fl
LysM-Cre mice, respectively as well as thrombocytopenia in
ADAP
fl/fl
PF4-Cre mice. Active EAE was induced in these animals by immunization with the myelin oligodendrocyte glycoprotein
35-55
peptide. The clinical course of EAE was significantly milder in mice with loss of
ADAP
in T cells, myeloid cells and NK cells compared to
ADAP
-sufficient control littermates. Surprisingly, specific deletion of
ADAP
in platelets resulted in a more exacerbated disease. These data show that T cell-independent as well as T cell-dependent mechanisms are responsible for the complex phenotype observed in conventional
ADAP
knockout mice.
...
PMID:Immune Cell-Type Specific Ablation of Adapter Protein ADAP Differentially Modulates EAE. 3163 10
